Immunogenetics: achieving new heights by immunohistochemistry; newer immunohistochemical markers of value in surgical pathology

Abstract

Immunogenetics refers to the use of immunohistochemical staining to reflect the underlying genetic alterations. The potential applications are: (1) understanding basic mechanism of disease or tumour; (2) aid in diagnosis; and (3) aid in prognostication. This is a simple and inexpensive way to infer the presence of specific molecular alterations. <b>Specific chromosomal translocations in tumours</b>: Examples include follicular lymphoma (BCL2); mantle cell lymphoma (Cyclin D1); tumours with ALK translocation (anaplastic large cell lymphoma, inflammatory myofibroblastic tumour); tumours with TFE-3 translocation (alveolar soft part sarcoma, and translocation carcinoma of kidney). <b>Specific mutations in tumours</b>: Examples include β-catenin gene mutation (such as solid-pseudopapillary tumour of pancreas), as reflected by abnormal nuclear translocation of the protein; p53, with extensive strong staining indicating presence of <i>P53</i> mutation, such as serous carcinoma of uterus. <b>Gene deletion or loss of function, as reflected by loss of staining</b>: Examples include mismatch repair gene proteins (colorectal cancer with microsatellite instability); E-cadherin (lobular neoplasm of breast); INI-1 (rhabdoid tumour). <b>Gene amplification</b>: Example: HER2 in breast cancer. <b>Surrogate markers</b>: Examples include expression of p16 in cervical epithelium as marker for high-risk HPV; ZAP-70 as marker for the unmutated group of CLL (worse prognosis).